Although it is known that ketone bodies are readily utilized for energy production by developing rat brain, a precursor-role of ketone bodies for cerebral lipid synthesis is not clear. Using cerebral cortex slices from one-week-old rats the incorporation of labeled ketone bodies and glucose into lipids will be investigated. The specific aims of this study are (1) to investigate an interaction and regulation of ketone bodies and glucose for the biosynthesis of lipids by rat brain during the postnatal period, and (2) to investigate whether the proposed 'cytosolic pathway' for the metabolism of acetoacetate operates in the brain. In the latter approach specific metabolic inhibitors such as n-butylmalonate and benzene 1,2,3-tricarboxylate for the citrate transporter system and (-) hydroxycitrate for ATP-citrate lyase will be used to investigate a possible existence of a cytosolic pathway for conversion of acetoacetate to acetyl-CoA in rat brain cytosol. In addition to gain some information on a possible impairment in the metabolism of ketone bodies in brains of affected patients with maple-syrup urine disease, the effect of leucine and a-ketoisocaproate on the metabolism in vitro of ketone bodies and glucose by developing rat brain will be investigated. BIBLIOGRAPHIC REFERENCES: Patel, M.S. and Owen, O.E. Effect of hyperphenylalaninemia on lipid synthesis from ketone bodies by rat brain. Biochem. J. (1976) in press. Patel, M.S. Citrate transport and oxidation by isolated rat brain mitochondria. Brain Res. 98 (1975) 607-611.